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Quinine Inhibits Mitochondrial ATP-regulated Potassium Channel from Bovine Heart

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Abstract

The mitochondrial ATP-regulated potassium (mitoKATP) channel has been suggested as trigger and effector in myocardial ischemic preconditioning. However, molecular and pharmacological properties of the mitoKATP channel remain unclear. In the present study, single-channel activity was measured after reconstitution of the inner mitochondrial membrane from bovine ventricular myocardium into bilayer lipid membrane. After incorporation, a potassium-selective current was recorded with mean conductance of 103 ± 9 pS in symmetrical 150 mM KCl. Single-channel activity of this reconstituted protein showed properties of the mitoKATP channel: it was blocked by 500 μM ATP/Mg, activated by the potassium-channel opener diazoxide at 30 μM, inhibited by 50 μM glibenclamide or 150 μM 5-hydroxydecanoic acid, and was not affected by the plasma membrane ATP-regulated potassium-channel blocker HMR1098 at 100 μM. We observed that the mitoKATP channel was blocked by quinine in the micromolar concentration range. The inhibition by quinine was additionally verified with the use of 86Rb+ flux experiments and submitochondrial particles. Quinine inhibited binding of the sulfonylurea derivative [3H]glibenclamide to the inner mitochondrial membrane. We conclude that quinine inhibits the cardiac mitoKATP channel by acting on the mitochondrial sulfonylurea receptor.

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Acknowledgments

This study was supported in part by the Polish State Committee for Scientific Research under grants No. 6P04A02321, 6P04A01019 and by a grant of the Roche Organ Transplantation Research Foundation (ROTRF 860428181). This study was also supported partially by NATO collaborative grant LST.CLG.979217 and a grant from the Agricultural University SGGW No. 50406020013.

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Authors and Affiliations

  1. Department of Biophysics, Agricultural University SGGW, 26/30 Rakowiecka St., 02-528, Warszawa, Poland

    P. Bednarczyk & K. Dolowy

  2. Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warszawa, Poland

    P. Bednarczyk, A. Kicińska & A. Szewczyk

  3. Laboratory of Intracellular Ion Channels, Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 83334, Bratislava, Slovak Republic

    V. Kominkova & K. Ondrias

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  1. P. Bednarczyk
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  2. A. Kicińska
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Correspondence to A. Szewczyk.

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(P. Bednarczyk and A. Kicińska) These authors contributed equally to this work.

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Bednarczyk, P., Kicińska, A., Kominkova, V. et al. Quinine Inhibits Mitochondrial ATP-regulated Potassium Channel from Bovine Heart. J Membrane Biol 199, 63–72 (2004). https://doi.org/10.1007/s00232-004-0676-9

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